Volumes of cochlear nucleus regions in rodents.

The cochlear nucleus receives all the coded information about sound from the cochlea and is the source of auditory information for the rest of the central auditory system. As such, it is a critical auditory nucleus. The sizes of the cochlear nucleus as a whole and its three major subdivisions - anteroventral cochlear nucleus (AVCN), posteroventral cochlear nucleus (PVCN), and dorsal cochlear nucleus (DCN) - have been measured in a large number of mammals, but measurements of its subregions at a more detailed level for a variety of species have not previously been made. Size measurements are reported here for the summed granular regions, DCN layers, AVCN, PVCN, and interstitial nucleus in 15 different rodent species, as well as a lagomorph, carnivore, and small primate. This further refinement of measurements is important because the granular regions and superficial layers of the DCN appear to have some different functions than the other cochlear nucleus regions. Except for DCN layers in the mountain beaver, all regions were clearly identifiable in all the animals studied. Relative regional size differences among most of the rodents, and even the 3 non-rodents, were not large and did not show a consistent relation to their wide range of lifestyles and hearing parameters. However, the mountain beaver, and to a lesser extent the pocket gopher, two rodents that live in tunnel systems, had relative sizes of summed granular regions and DCN molecular layer distinctly larger than those of the other mammals. Among all the mammals studied, there was a high correlation between the size per body weight of summed granular regions and that of the DCN molecular layer, consistent with other evidence for a close relationship between granule cells and superficial DCN neurons.

Conventional open repair of descending thoracic aortic aneurysms.

Conventional open reconstruction of the descending thoracic aorta is a safe and effective therapy for the management of aneurysms and is the standard by which all other therapies should be compared. Advances in surgical techniques, circulation management, neurocerebral protection, anesthesia, and postoperative management have contributed to significant reductions in morbidity and mortality over the past 50 years. More recently, endovascular stent grafting has begun to supplant conventional open repair based on its ease of performance and a perception of reduced morbidity and mortality. In reality, when carefully compared, differences in primary outcomes (mortality, stroke rate, and paraplegia) between open repair and endovascular repair are not so clear, and the long-term durability of endovascular repairs is not yet known. Open descending thoracic aortic repair still has an important role in the management of descending thoracic aortic disease in the current era.

Forceful evacuation of retained pneumoperitoneum mimics an acute recurrent inguinal hernia.

BACKGROUND: Laparoscopic exploration of the contralateral side during inguinal herniorrhaphy in infants is becoming popular. We present an unusual complication of this technique, namely forceful evacuation of retained pneumoperitoneum mimicking an acute recurrent hernia. METHODS: A 9-month-old female presented for right inguinal herniorrhaphy. Laparoscopic exploration of the left side revealed a closed left internal ring. The pneumoperitoneum was evacuated. The hernia sac had started to tear so it was closed with a running horizontal mattress suture instead of a double ligature after twisting. The internal ring was closed. Upon emergence from anesthesia, the right groin was filled with a mass that we felt was subcutaneous emphysema from evacuation of residual pneumoperitoneum. But to rule out an acute recurrent hernia, we re-explored the groin. There was a large collection of air that had dissected in the subcutaneous tissues and under Scarpa's fascia. The hernia repair was intact. Follow-up 6 months after the repair showed no evidence of a recurrence. RESULTS: This is the first report of an unusual complication of laparoscopic exploration of the contralateral side during hernia repair. Two factors contributed to it. The sac closure was a running mattress suture, which is not as airtight as a double ligature after twisting. The second is the incomplete evacuation of the pneumoperitoneum. CONCLUSION: With the increasing use of laparoscopic contralateral exploration, this case illustrates the need to evacuate the pneumoperitoneum as thoroughly as possible and to consider an airtight closure of the sac.

Role of the thymus and kidney graft in the maintenance of tolerance to heart grafts in miniature swine.

BACKGROUND: The authors have examined the mechanism whereby co-transplantation of a kidney and heart from the same donor induces and maintains tolerance to both organs in miniature swine. METHODS: Transplants were performed across a major histocompatibility complex class I mismatch, and recipients received cyclosporine for 12 days. Group 1 animals received heart transplants alone (n=5), and all other groups received both heart and kidney allografts. Group 2 animals received no further intervention (n=2). Group 3 animals underwent transplant nephrectomy 8 days after heart and kidney co-transplantation (n=2). Group 4 animals underwent transplant nephrectomy 100 days after co-transplantation (n=2). Skin grafts were placed on group 4 animals, on one group 3 animal, and on two animals from group 2. Group 5 animals underwent thymectomy 100 days after co-transplantation (n=4). RESULTS: Group 1 animals developed cardiac allograft vasculopathy (CAV) and rejection. Group 2 animals never developed CAV and demonstrated in vitro donor-specific unresponsiveness. Group 3 animals suffered CAV and rejection. Group 4 animals developed CAV without concomitant donor-specific cell-mediated lympholysis reactivity, interstitial rejection, or cessation of graft function. Skin grafts on group 3 and group 4 animals led to fulminant rejection of heart and skin grafts, in contrast to grafts on group 2 animals that had no in vivo effect. Group 5 animals developed CAV but no significant increase in interstitial infiltrates. CONCLUSIONS: Both the kidney and thymus were necessary for maintenance of tolerance to heart allografts.

Indirect recognition of MHC class I allopeptides accelerates lung allograft rejection in miniature swine.

The role of indirect allorecognition in graft rejection is examined in two experiments using a swine lung transplantation model. First, two swine received class I mismatched grafts without immunosuppression; another two recipients were treated postoperatively with cyclosporine (CsA). These swine exhibited acute and chronic rejection, respectively. All four recipients developed T-cell reactivity to donor-derived class I major histocompatibility complex (MHC) peptides. Second, six swine were immunized with synthetic donor-derived class I allopeptides prior to transplantation. Control groups consisted of nonimmunized recipients (n = 6) and recipients immunized with an irrelevant peptide (n = 3). These recipients all received a 12-day course of post-operative CsA. Swine immunized with allopeptides exhibited accelerated graft rejection, as compared to both control groups (p < 0.01 and p = 0.03, respectively). Within the experimental group, the dominant histologic finding was acute rejection (AR). Obliterative bronchiolitis (OB) was seen in the graft with the longest survival. Both control groups showed a lesser degree of AR, with four out of six nonimmunized swine ultimately developing OB. These studies suggest that indirect allorecognition is operative during lung allograft rejection, and that pre-transplant sensitization to donor-derived MHC allopeptides can accelerate graft rejection.

Constitutive expression of major histocompatibility complex class II antigens in pulmonary epithelium and endothelium varies among different species.

We have observed high constitutive levels of class II antigen expression on porcine and human coronary endothelium, but not on the endothelium of rats and mice. This study examines whether a similar interspecies difference exists in the expression of class II molecules on pulmonary epithelium and endothelium. Lung tissues from naïve human, porcine, and rodent sources were stained with the monoclonal antibody ISCR3 and examined by light microscopy. Immunoperoxidase staining of class II molecules was observed on human and porcine pulmonary epithelium and endothelium, but was absent in rats and mice. By using an antibody with cross-species reactivity, we demonstrated that naïve swine pulmonary epithelium and endothelium, unlike those of rodent species, express basal levels of class II antigens in a manner similar to that observed in human lung tissue. These interspecies differences may explain experimental differences observed between murine and large-animal constructs.

Nonoperative management of neonatal splenic rupture.

Neonatal injury of the spleen is an uncommon but serious condition. Although the standard management of children with splenic injury is nonoperative, there is scant evidence in the literature to support handling neonates in the same way. We report a case of neonatal splenic rupture that was managed nonoperatively. A 3.6-kg full-term female born vaginally became tachycardic and pale on the second day of life. She had a distended abdomen and a hemoglobin of 5.8 g/dL. Her blood pressure remained within normal limits. She was transfused 20 cc/kg packed red blood cells. CT scan showed a grade V splenic rupture. Coagulopathy workup was negative. The assumption was that she had a ruptured spleen secondary to a traumatic delivery. She remained stable after the transfusion. It took 32 weeks for a CT scan to show complete healing. Traditionally, neonatal splenic rupture has been treated with splenectomy or splenorrhaphy. The first case of a neonate to be treated nonoperatively was reported in 2000. Our patient is only the second reported case. We chose to follow her with imaging to document healing and to rule out a tumor, as epidermoid cysts and hemangioendotheliomas can cause neonatal splenic rupture. We also review the literature to try to gain some insight into the management of this rare problem.

Induction of tolerance to heart transplants by simultaneous cotransplantation of donor kidneys may depend on a radiation-sensitive renal-cell population.

BACKGROUND: To determine the mechanism by which cotransplantation of a donor kidney and heart allograft induces tolerance to both organs in miniature swine, we examined the renal elements responsible for tolerance induction. METHODS: Recipients received 12 days of cyclosporine, and transplants were performed across a major histocompatibility complex (MHC) class I mismatch. Group 1 animals received heart transplants (n=5); group 2 animals received heart and kidney allografts with no other manipulation (n=4); group 3 animals received heart transplants and donor-specific renal parenchymal cells (n=4); group 4 animals received heart and kidney allografts from lethally irradiated donors (n=7); group 5 animals received irradiated hearts and nonirradiated kidneys (n=2); group 6 animals received nonirradiated hearts and peripheral blood leukocytes from swine MHC matched to recipients and becoming tolerant to donor antigen (n=2); group 7 animals received nonirradiated hearts and donor-specific peripheral blood monocyte cells (PBMC) (n=2). RESULTS: Animals in group 1 developed vasculopathy and fulminant rejection by day 55. Animals in group 2 never developed vascular lesions. Parenchymal kidney cell infusion (group 3) did not prolong cardiac survival. Animals in group 4 developed arteriopathy by postoperative day (POD) 28. Group 5 recipients accepted allografts without vascular lesions. Adoptive transfer of leukocytes from tolerant swine (group 6) prolonged cardiac graft survival as much as 123 days, whereas donor PBMC infusion (group 7) did not affect cardiac survival or development of arteriopathy. CONCLUSIONS: Radiosensitive elements in kidney allograft may be responsible for tolerance induction and prevention of chronic vascular lesions in recipients of simultaneous heart and kidney allografts.

Modeling chronic lung allograft rejection in miniature swine.

BACKGROUND: The success of lung transplantation has been limited by the perplexing problem of chronic rejection. The development of a large-animal model for the systematic study of the mechanisms underlying chronic lung rejection has been problematic. We have developed a new preclinical model of chronic lung rejection using MHC-inbred miniature swine. METHODS: Using standard operative techniques, four orthotopic left lung allografts were performed using MHC-matched, minor-antigen-mismatched donors. Recipient animals received a 12-day course of postoperative cyclosporine. Grafts were followed with open biopsies and high-resolution computed tomography. Cellular immune responses were monitored by mixed lymphocyte reaction, cytometric analysis of graft-infiltrating lymphocytes, and skin grafting. RESULTS: All grafts survived > or = 5 months and developed manifestations of chronic rejection, including obliterative bronchiolitis, interstitial fibrosis, and occlusive vasculopathy. A mononuclear infiltrate was also present in all grafts by the fourth posttransplant month. High-resolution computed tomography demonstrated several cardinal radiographic findings known to correlate with chronic rejection. Cytometric analysis of graft-infiltrating lymphocytes showed a predominance of CD8+ cells. The development of alloreactivity in the host was confirmed by mixed lymphocyte reaction and skin grafting. CONCLUSIONS: We report a reproducible, whole-lung, large-animal model of chronic lung rejection. In this immunogenetically defined construct, we have observed a full spectrum of histopathologic lesions that reproduce with fidelity those lesions observed in human lung transplant recipients suffering from chronic rejection. We anticipate that this preclinical model will facilitate further study of the pathogenesis and therapy of chronic lung rejection.

Cytokines in immunity and allograft rejection.

Cytokines are highly potent regulatory molecules that are secreted by a variety of cells into the local microenvironment. These chemical messengers participate in the activation and regulation of immune function by a variety of mechanisms, including the stimulation and inhibition of cellular proliferation and differentiation. Cytokines also may have chemotactic activity. Six cytokine receptor families have been described, on the basis of their conserved structural features. Many cytokines are classified as proinflammatory cytokines, which promote both innate and adaptive immune responses. Solid-organ transplantation presents several unique challenges to the immune system, and cytokines play an important role in both antigen-dependent and antigen-independent immune recognition. The selective blockade of cytokine-mediated immune responses is a cornerstone of modern immunosuppressive therapy.